2. Academic Validation
  3. Long noncoding RNA TUG1 promotes malignant progression of osteosarcoma by enhancing ZBTB7C expression

Long noncoding RNA TUG1 promotes malignant progression of osteosarcoma by enhancing ZBTB7C expression

  • Biomed J. 2023 Aug 8;100651. doi: 10.1016/j.bj.2023.100651.
Xueying An 1,  Wenshu Wu 1,  Pu Wang 2,  Abdurahman Mahmut 2,  Junxia Guo 3,  Jian Dong 2,  Wang Gong 2,  Bin Liu 2,  Lin Yang 3,  Yuze Ma 2,  Xingquan Xu 4,  Jianmei Chen 5,  Wangsen Cao 6,  Qing Jiang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China; Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, China.
  • 3 Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: xuxingquan12345@163.com.
  • 5 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. Electronic address: cjm@yzu.edu.cn.
  • 6 Nanjing University Medical School, Jiangsu Key Lab of Molecular Medicine. Nanjing, China; Department of Central Laboratory, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, China. Electronic address: wangsencao@nju.edu.cn.
  • 7 State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China; Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, China. Electronic address: qingj@nju.edu.cn.
PMID: 37562773 DOI: 10.1016/j.bj.2023.100651
Abstract

Background: Dysregulation of long non-coding RNAs (lncRNAs) is an important component of tumorigenesis. Aberrant expression of lncRNA taurine upregulated gene 1 (lncTUG1) has been reported in various tumors; however, its precise role and key targets critically involved in osteosarcoma (OS) progression remains unclear.

Methods: The expression profiles of lncRNAs and its regulated miRNAs related to OS progression were assessed by bioinformatics analysis and confirmed by qRT-PCR of OS cells. The miRNA targets were identified by transcriptome Sequencing and verified by luciferase reporter and RNA pull-down assays. Several in vivo and in vitro approaches, including CCK8 assay, western blot, qRT-PCR, lentiviral transduction and OS cell xenograft mouse model were established to validate the effects of lncTUG1 regulation of miRNA and the downstream target genes on OS cell growth, Apoptosis and progression.

Results: We found that lncTUG1 and miR-26a-5p were inversely up or down-regulated in OS cells, and siRNA-mediated lncTUG1 knockdown reversed the miR-26a-5p down-regulation and suppressed proliferation and enhanced Apoptosis of OS cells. Further, we identified that an oncoprotein ZBTB7C was also upregulated in OS cells that were subjected to lncTUG1/miR-26a-5p regulation. More importantly, ZBTB7C knockdown reduced the ZBTB7C upregulation and ZBTB7C overexpression diminished the anti-OS effects of lncTUG1 knockdown in the OS xenograft model.

Conclusions: Our data suggest that lncTUG1 acts as a miR-26a-5p Sponge and promotes OS progression via up-regulating ZBTB7C, and targeting lncTUG1 might be an effective strategy to treat OS.

Keywords

Apoptosis; LncTUG1; Osteosarcoma; ZBTB7C; miR-26a-5p.

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